Effect of Midazolam Alone Versus Midazolam with Maternal Presence on Pain and Anxiety of Lumbar Puncture in 6 to 24-Month-Old Children.

Objectives Midazolam at a dosage of 0.5 mg/kg induces anxiolytic effects in 90% of children. This study was performed to elucidate whether intravenous midazolam with maternal presence is more efficient than intravenous midazolam alone in the reduction of pain and anxiety of lumbar puncture (LP) in 6 to 24-month-old children. Materials & Methods In this not-blinded clinical trial, we included 60 children aged 6 to 24 months old undergoing LP in the Pediatric Ward of Shahid Sadoughi Hospital, Yazd, Iran, from September 2014 to March 2015. The participants were randomly assigned to two groups, and all of them received painless injection of 0.5 mg/kg midazolam five minutes before LP. In group I, LP was performed with maternal presence and in group II, the mothers were absent. The primary outcomes included anxiety and pain scores before LP and during needle insertion to the skin for LP. The secondary outcomes comprised of success rates in the reduction of anxiety (anxiety score of four and more) and pain (pain score of less than three) when the needle was inserted to the skin for LP. Results Twenty-eight girls and 32 boys were evaluated in the two groups. Maternal presence was found to be effective in the reduction of anxiety (2.7±0.65 vs. 3.83±0.87; P=0.001) and pain scores (3.8±1.75 vs. 6.1±1.63, P=0.001). In the maternal presence group, success rate in anxiety (76.7% vs. 16.6%; P=0.0001) and pain reduction (63.3 % vs. 6.7%; P=0.0001) was higher than in the midazolam alone group. Conclusion Maternal presence during lumbar puncture can reduce pain and anxiety among 6 to 24-month-old children.


Introduction
Untreated pain can negatively affect the development of the central nervous system (CNS), which has long-standing psychological consequences (1). Lumbar puncture (LP) is a painful diagnostic procedure which can help in the detection of CNS infections, subarachnoid hemorrhage, brain tumors and demyelinat ingdegenerative disorders (2). Midazolam is a medication with rapid onset of action and little adverse events, which can be used via oral, intravenous, intranasal and intramuscular routes of administration, and it has been used as a sedative before medical procedures for many years. Cochrane Database systematic review showed that intravenous midazolam in comparison with placebo decreased the anxiety of diagnostic and therapeutic medical procedures (7).
Midazolam is a short-acting, potent, hypnotic and anxiolytic drug most commonly used in pediatric anesthesia and induces anxiolytic effects in 90% of children at a dosage of 0.5 mg/kg (8). Different procedural sedation regimens have been used in different pediatric departments and we use 0.5 g/ kg intravenous midazolam for sedation before LP in our department.
Up until mid-1990s, parental presence during invasive procedures was not adhered to or widely accepted (9), and medical staff, especially nurses disagreed to paternal presence during medical invasive procedures (9,10). Nonetheless, nurses believe that the presence of family reduces children's distress and parental anxiety (10).

Materials & methods
In this randomized, not-blinded, parallel-group clinical trial, we enrolled all the consecutive 6 to Based on Z formula and with a confidence interval of 95% , power of 80%, type one error of 5%, success in anxiety reduction (obtaining anxiety score of more than 4 during LP) of 52% for maternal presence in our pilot study and an effect size (difference in frequency of success in anxiety reduction between the two groups) of 30% for this primary outcome, the sample size was calculated to be 30 children in each group.
The inclusion criteria comprised of children The developmental status of the children was assessed using the Denver II Developmental Screening Test. We used computer-generated equal simple randomization by random numbers, and the allocation ratio was 1:1 for the two groups.
Since the mothers were present during LP in the maternal presence group and the resident of research who assessed the primary and secondary outcomes and gathered the data and the resident of research who did LP were seeing the mothers, blinding of the participating mothers, pediatric resident, data collector and outcome assessor was not possible, and only the data analysts were kept blinded to the allocation. However, concealment was performed by placing the group number for each serially participating child in a numbered and sealed opaque envelope which was opened by the pediatric neurologist immediately before LP. Randomization and concealment were done by a researcher with no clinical involvement in the trial.
In both groups, 0.5 mg/kg midazolam was injected intravenously five minutes before LP and the children were randomly assigned to the two groups.
In group I, lumbar puncture was performed with maternal presence, and in group II, the mothers were out of the room during LP of their children.

Results
The design and conduct of this trial were straightforward, and we did not have any losses or exclusions from the analysis. Overall, 28 girls and 32 boys with the mean age of 1.06 ± 0.43 year were evaluated in the two groups. Based on the Kolmogorov-Smirnov test, the data had normal distribution.
Comparison of some characteristics of the children in the two groups is presented in Table 1, which indicates that no significant differences were observed in terms of gender distribution, mean age, mean weight, mean anxiety or pain score before LP. Table 2 shows the comparison of anxiety and pain scores during LP and the frequency of traumatic lumbar puncture in the two groups, which indicates that maternal presence was effective in the reduction of anxiety and pain scores of the children during LP, but the frequency of traumatic LP was not significantly different between the groups. Comparison of frequencies of success rate in reducing anxiety (obtaining an anxiety score of four and more) and pain (pain score of less than three) during skin needle insertion for LP is presented in Table 3. This table demonstrates that in the maternal presence group, the success rate in anxiety and pain reduction was more than in the midazolam alone group.
In the present study, maternal presence did not increase the rate of traumatic LP, which is compatible with the results of a previous study that indicated family presence did not increase the risk of traumatic or unobtainable LP (19).
The efficacy of family presence during resuscitation and invasive medical procedures was evaluated by Mangurten et al (20). Care of sick children was not disturbed by paternal presence and parents who were affirmative about their presence thought that it assisted their kids and assumed that it alleviated their anxiety. The parents reported an active role during the event, and most of them stated that they were rightful to be present. None of the parents reported traumatic memories after three months (20).
In order to implement pediatric departments' parental presence protocol, first it is essential to identify the positive effects of family presence (21) to accept the presence of parents during invasive procedures. Then, parents should be given the option to be present during invasive medical procedure of their sick children (18).
In conclusion, Based on the results of this randomized clinical trial, the combination of maternal presence during LP with intravenous midazolam could reduce pain and anxiety of lumbar puncture in 6 to 24-month-old children.